SERUM FETUIN-A LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is the second most common rheumatic disease. In recent decades, there has been an active search for and study of biologically active substances involved in the pathogenesis of RA, which can serve as a starting point in designing new drugs for targeted therapy of this disease. The hepatokine fetuin-A (FA) is one of these substances.
Objective: to investigate serum FA levels in patients with RA.
Subjects and methods. The investigation enrolled 110 patients with RA. All the patients underwent the following set of studies: general blood test and determination of the serum levels of C-reactive protein (CRP), serum FA, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage degradation products (CartiLaps), and urine creatinine. A control group consisted of 30 apparently healthy individuals whose serum FA level was determined in order to obtain reference values.
Results and discussion. The normal FA level varied from 653.55 to 972.19 μg/ml. All the patients with RA were divided into two groups: 1) 23 patients with a low FA level (<653.55 μg/ml) and 2) 87 patients with a normal FA levels (≥653.55 μg/ml). The groups differed significantly in anti-CCP antibody concentrations, disease activity, radiological stages, functional classes, and the presence of complications. Patients with lower FA levels were noted to have increased CRP concentrations, erythrocyte sedimentation rate, and CartiLaps/urine creatinine ratio. The mean FA concentration was considerably and significantly lower in patients with higher DAS28 scores. 
Conclusion. Our investigation has revealed that there is a relationship between the levels of FA and the individual clinical manifestations of RA. The lower FA level is associated with higher disease activity and the aggressive phenotype of RA (the presence of anti-CCP antibodies, radiological stages III and IV, extra-articular manifestations and complications).

1. Nasonov EL, Karateev DE. Rheumatoid arthritis. In: Rossiyskiye klinicheskiye rekomendatsii. Revmatologiya [Russian clinical recommendations. Rheumatology]. Moscow: GEOTAR-Media; 2017. P. 17-57 (In Russ.).

2. Zborovskaya IA, Zavodovskiy BV, Akhverdyan YuR, et al. Prognostic value of determining the level of leptin in workers of industrial enterprises of Volgograd with osteoarthritis. Meditsina Truda i Promyshlennaya Ekologiya = Labor Medicine and Industrial Ecology. 2013;(1):34-8 (In Russ.).

3. Akhverdyan YuR, Zavodovskiy BV, Polyakova YuV, et al. Nicotinamide-phosphoribosyltransferase as a marker of systemic inflammation in osteoarthritis. Klinicheskaya Laboratornaya Diagnostika = Clinical Laboratory Diagnostics. 2017;62(10):606-10 (In Russ.). doi: 10.18821/0869-2084-2017-62-10-606-610

4. Sivordova LE, Polyakova YuV, Zavodovskiy BV, et al. Resistin as a pathogenetic factor in the development of osteoarthritis. Doctor.Ru. 2013;6(84):58-61 (In Russ.).

5. Pederson KO. Fetuin, a new globulin isolated from serum. Nature. 1944;154:575.

6. Mukhopadhay S, Mondal SA, Kumar M, et al. Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome. Endocr Pract. 2014;20(12):1345-51. doi: 10.4158/EP14421.RA

7. Wang H, Tracey KJ. Fetuin opsonizes macrophage-deactivating cations. In: Marshall JC, Cohen J, eds. Update in Intensive Care and Emergency Medicine: Immune Response in the Critically Ill. Springer Verlag Press; 1999. P. 155-63.

8. Bilgir O, Kebapcilar L, Bilgir F, et al. Decreased serum fetuin-A levels are associated with coronary artery diseases. Intern Med. 2010;49(13):1281-5. doi: 10.2169/internalmedicine.49.3223

9. Dabrowska AM, Tarach JS, Wojtysiak-Duma B, et al. Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159(3):352-9. doi: 10.5507/bp.2015.018

10. Daveau M, Christian D, Julen N, et al. The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines on hepatoma HepG2 cells. FEBS Lett. 1988;241(1-2):191-4. doi: 10.1016/0014-5793(88)81059-7

11. Wang H, Sama AE. Anti-inflammatory role of fetuin-A in injury and infection. Curr Mol Med. 2012;12:625-33. doi: 10.2174/156652412800620039

12. Xiao J, Wang X, Hu K, et al. Serum fetuin-A levels are inversely associated with clinical severity in patients with primary knee osteoarthritis. Biomarkers. 2013;18(1):51-4. doi: 10.3109/1354750X.2012.730551

13. Ozturk S, Keser M, Kozaci D, et al. Fetuin-A and its association with disease activity on psoriatic arthritis. Ann Rheum Dis. 2014;73:207. doi: 10.1136/annrheumdis-2014-eular.4473

14. Sato H, Kazama JJ, Wada Y, et al. Decreased levels of circulating α2-Heremans-Schmid glycoprotein/Fetuin-A (AHSG) in patients with rheumatoid arthritis. Intern Med. 2007;46:1685-92. doi: 10.2169/internalmedicine.46.6269

15. Li W, Zhu S, Li J, et al. A hepatic protein, fetuin-a, occupies a protective role in lethal systemic inflammation. PLoS One. 2011;6(2):e16945. doi: 10.1371/journal.pone.0016945

16. Inoue K, Ikeda Y, Yamanaka S, et al. Serum fetuin-A levels in patients with rheumatoid arthritis. 77th congress of the European atherosclerotic society, 2008.

17. Harman H, Tekeoglu I, Gurol G, et al. Comparison of fetuin-A and transforming growth factor beta 1 levels in patients with spondyloarthropathies and rheumatoid arthritis. Int J Rheum Dis. 2016;20(12):2020-7. doi: 10/1111/1756-185X.12791

18. Tekeoglu I, Harman H, Sag S, et al. Levels of serum pantraxin 3, IL-6, fetuin A and insulin in patients with rheumatoid arthritis. Cytokine. 2016;83:171-5. doi: 10.1016/j.cyto.2016.04.009

19. Mauviel A. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem. 1993;53:288-95. doi: 10.1002/jcb.240530404

20. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006;11:529-43. doi: 10.2741/1817